tbuckley/cabot-search huggingface dataset:
Anatomical resection improves relapse-free survival in colorectal liver metastases in patients with KRAS/NRAS/BRAF mutations or right-sided colon cancer: a retrospective cohort study
Authors: Wenju Chang, Yijiao Chen, Shizhao Zhou, Li Ren, Yuqiu Xu, Dexiang Zhu, Wentao Tang, Qinghai Ye, Xiaoying Wang, Jia Fan, Ye Wei, Jianmin Xu
Journal: International Journal of Surgery (2023)

The type of liver resection (anatomical resection, AR or non-anatomical resection, NAR) for colorectal liver metastases (CRLM) is subject to debate. The debate may persist because some prognostic factors, associated with aggressive tumor biological behavior, have been overlooked.Our study aimed to investigate the characteristics of patients who would benefit more from anatomical resection for CRLM.Seven hundred twenty-nine patients who underwent hepatic resection of CRLM were retrospectively collected from June 2012 to May 2019. Treatment effects between AR and NAR were compared in full subgroup analyses. Tumor relapse-free survival (RFS) was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods.Among 729 patients, 235 (32.2%) underwent AR and 494 (67.8%) underwent NAR. We showed favorable trends in RFS for AR compared with NAR in the patients with KRAS/NRAS/BRAF mutation (interaction P <0.001) or right-sidedness (interaction P <0.05). Patients who underwent AR had a markedly improved RFS compared with NAR in the cohorts of RAS/NRAS/BRAF mutation (median RFS 23.2 vs. 11.1 months, P <0.001) or right-sidedness (median RFS 31.6 vs. 11.5 months, P <0.001); upon the multivariable analyses, AR [gene mutation: hazard ratio (HR)=0.506, 95% CI=0.371-0.690, P <0.001; right-sidedness: HR=0.426, 95% CI=0.261-0.695, P =0.001) remained prognostic independently. In contrast, patients who underwent AR had a similar RFS compared with those who underwent NAR, in the cohorts of patients with gene wild-type tumors (median RFS 20.5 vs. 21.6 months, P =0.333). or left-sidedness (median RFS 15.8 vs. 19.5 months, P =0.294).CRLM patients with gene mutation or right-sidedness can benefit more from AR rather than from NAR.
Alexithymia prevalence in individuals with chronic urticaria and its association with illness severity and therapeutic profile
Authors: Ivan Cherrez-Ojeda, Simon Francis Thomsen, Ana Giménez-Arnau
Journal: British Journal of Dermatology (2023)

Forty-two per cent of patients with chronic urticaria in our study had alexithymia. Female patients had approximately 48% higher odds of having alexithymia. Patients with uncontrolled urticaria had 58% higher odds of having alexithymia. Among those with mild urticaria activity, the likelihood of having alexithymia was twice that of urticaria-free individuals. The use osf older first-generation antihistamines doubled the odds of having alexithymia. Patients with chronic urticaria with cardiovascular comorbidities had a 2.5-fold increased risk of alexithymia.
Diversifying the Genetic Landscape of Heart Disease
Authors: Catherine Tcheandjieu, Thomas P. Cappola
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis
Authors: Haibo Ni, Stefano Morotti, Xianwei Zhang, Dobromir Dobrev, Eleonora Grandi
Journal: Cardiovascular Research (2023)

Atrial fibrillation (AF), the most prevalent clinical arrhythmia, is associated with atrial remodelling manifesting as acute and chronic alterations in expression, function, and regulation of atrial electrophysiological and Ca2+-handling processes. These AF-induced modifications crosstalk and propagate across spatial scales creating a complex pathophysiological network, which renders AF resistant to existing pharmacotherapies that predominantly target transmembrane ion channels. Developing innovative therapeutic strategies requires a systems approach to disentangle quantitatively the pro-arrhythmic contributions of individual AF-induced alterations.
Sepsis, a call for inclusion in the work plan of the European Center for Disease Prevention and Control
Authors: Evangelos J. Giamarellos-Bourboulis, Annelies S. Zinkernagel, Edoardo De Robertis, Élie Azoulay, Daniele De Luca, Antonio Artigas, Luregn J Schlapbach, Ron Daniels, Konrad Reinhart, Konrad Reinhart, Jesús Rodríguez Baño, Kai Zacharowski, Maurizio Cecconi
Journal: Intensive Care Medicine (2023)

Sepsis is a devastating condition resulting from our bodies' dysregulated immune system response to infections, which can lead to organ failure, death, or sometimes lifelong disability.Common infections with bacterial, fungal and viral diseases or as a consequence of injury, can cause sepsis.In addition, emerging infectious diseases either directly cause sepsis or predispose to sepsis.In the case of coronavirus disease 2019 (COVID-19), 52% of hospitalized patients in the wards and 78% of hospitalized patients in an intensive care unit meet the Sepsis-3 definitions [1].Sepsis affects all age groups, the highest incidence is seen at the extremes of age, neonates and young children [2], and the elderly.Each year, sepsis affects close to 50 million people globally, of whom 11 million die and more than half suffer long-term consequences such as physical or mental disabilities.In the European Union (EU), estimates extrapolated from a Swedish study of 2015 suggest that more than 3 million people suffer from sepsis each year resulting in 680,000 deaths [3].The incidence of sepsis is only second to cancer (2,681,958 cases with 1,261,722 deaths) [4].Across EU countries, stroke accounted for 375,000 deaths in 2017 [5].In 2016, 542,700 were due to coronary diseases, including heart attacks [6].Antimicrobial resistance (AMR) is another well-known health threat and priority for health authorities: each year more than 670,000 infections are due to bacteria resistant to antibiotics and approximately 33,000 people die as a direct consequence [7].However, many studies indicate that the number of deaths due to sepsis as well as the burden of post-sepsis morbidity and resultant costs for health care systems are grossly underestimated, also due to a lack of accurate data collection.
Medical Editors vs Nuclear Weapons—Is the Pen Mightier Than the Sword?
Authors: James E. Muller, Joseph Gold Hodgkin
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Germ Granule Evolution Provides Mechanistic Insight into <i>Drosophila</i> Germline Development
Authors: Dominique A Doyle, Florencia N Burian, Benjamin Aharoni, Annabelle J Klinder, Melissa M Menzel, Gerard Carlo C Nifras, Ahad L Shabazz-Henry, Bianca Ulrich Palma, Gisselle A Hidalgo, Christopher J Sottolano, Bianca M Ortega, Matthew G Niepielko
Journal: Molecular Biology and Evolution (2023)

Abstract The copackaging of mRNAs into biomolecular condensates called germ granules is a conserved strategy to posttranscriptionally regulate germline mRNAs. In Drosophila melanogaster, mRNAs accumulate in germ granules by forming homotypic clusters, aggregates containing multiple transcripts from the same gene. Nucleated by Oskar (Osk), homotypic clusters are generated through a stochastic seeding and self-recruitment process that requires the 3′ untranslated region (UTR) of germ granule mRNAs. Interestingly, the 3′ UTR belonging to germ granule mRNAs, such as nanos (nos), have considerable sequence variations among Drosophila species and we hypothesized that this diversity influences homotypic clustering. To test our hypothesis, we investigated the homotypic clustering of nos and polar granule component (pgc) in four Drosophila species and concluded that clustering is a conserved process used to enrich germ granule mRNAs. However, we discovered germ granule phenotypes that included significant changes in the abundance of transcripts present in species’ homotypic clusters, which also reflected diversity in the number of coalesced primordial germ cells within their embryonic gonads. By integrating biological data with computational modeling, we found that multiple mechanisms underlie naturally occurring germ granule diversity, including changes in nos, pgc, osk levels and/or homotypic clustering efficacy. Furthermore, we demonstrated how the nos 3′ UTR from different species influences nos clustering, causing granules to have ∼70% less nos and increasing the presence of defective primordial germ cells. Our results highlight the impact that evolution has on germ granules, which should provide broader insight into processes that modify compositions and activities of other classes of biomolecular condensate.
Endoscopic transvaginal drainage and necrosectomy of presacral walled-off pancreatic necrosis
Authors: Mia Prindahl Ærenlund, Lars Lindgaard, Srdan Novovic, Morten Laksáfoss Lauritsen, John Gásdal Karstensen, Palle Nordblad Schmidt
Journal: Endoscopy (2023)

Transluminal drainage and necrosectomy has become the preferred choice of treatment for complicated walled-off pancreatic necrosis (WON). Transgastric, transduodenal, transrectal, and transcolonic approaches have been described [1] [2] [3] [4], but in some cases the location of the WON prevents access through the gastrointestinal tract. We here describe a case of transvaginal drainage and necrosectomy.
Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study
Authors: Shubham Pant, Martin Schuler, Gopa Iyer, Olaf Witt, Toshihiko Doi, Shukui Qin, Josep Tabernero, David A Reardon, Christophe Massard, Anna Minchom, Iwona Lugowska, Omar Carranza, Dirk Arnold, Martin Gutierrez, Helen Winter, Kim Stuyckens, Lauren Crow, Saltanat Najmi, Constance Hammond, Shibu Thomas, Ademi Santiago-Walker, Spyros Triantos, Hussein Sweiti, Yohann Loriot, Omar Carranza, Martin Alberto Greco, Jim Coward, Anthony Joshua, Christos Karapetis, Christopher Hart, Alison Zhang, Hans Prenen, Jean-Charles Goeminne, Jean-Pascal Machiels, Sylvie Rottey, Marcelo Corassa, Graziela Zibetti Dal Molin, Katsuki Tiscoski, Denis Leonardo Fontes Jardim, Milena Mak, Wei Fu, Herui Yao, Jing Huang, Haiping Jiang, Shukui Qin, Baoshi Chen, Dong Yan, Yu Yang, Yohann Loriot, Christophe Le Tourneau, Nicolas Penel, Sébastien Salas, Jean-Yves Blay, Pierre-Emmanuel Brachet, Xavier Durando, Sheik Emambux, Alain Ravaud, Gunnar Folprecht, Dirk Arnold, Martin Schuler, Marit Ahrens, Alexander Golf, Georg Martin Haag, Florian Lordick, Alexander Desuki, Marina Cazzaniga, Fortunato Ciardiello, Michele Milella, Takafumi Koyama, Yoshiki Hirooka, Wataru Okamoto, Kenjiro Aogi, Yasutoshi Kuboki, Jungyun Lee, Sung-Bae Kim, Myung-Ju Ahn, Jong Hee Chang, Yong-Man Kim, Do-Hyun Nam, Jae-Sung Park, Iwona Lugowska, Luis Paz-Ares, Victor Moreno, Andres Cervantes, Mariona Calvo, Alejandro Falcon, Antonio Gonzalez, Josep Tabernero, Alejandro Martinez Bueno, Javier García-Corbacho, Federico Longo, Chia-Jui Yen, Jen-Shi Chen, Ming-Feng Hou, Yee Chao, Kun-Ming Rau, Tai-Jan Chiu, Yin-Hsun Feng, Chih-Hung Hsu, Wen-Tsung Huang, Kuan-Ming Lai, Su-peng Yeh, Daniel Palmer, Anna Minchom, Helen Winter, Liam Welsh, Ruth Plummer, Gopakumar Iyer, Martin Gutierrez, Mehmet Bilen, Edward Arrowsmith, Shubham Pant, David Robert Spigel, Dan Paul Zandberg, Deborah Doroshow, Christine Lu-Emerson, Mehdi Moezi, Scott Paulson, David Reardon, Patrick Ward, Jorge Chaves, Claud Grigg, Atif Hussein, Sudhir Manda, Michael Monticelli, Rubina Qamar, Stephen L Richey, David Tamura, Sharon Wilks
Journal: The Lancet Oncology (2023)
Vaccines for pregnant people: are we missing the forest for the trees?
Authors: Torri D Metz
Journal: The Lancet Digital Health (2023)

In their multicentre cohort study, Samantha Piekos and colleagues1 retrospectively assessed a large cohort of more than 100 000 pregnant patients, comparing those who received only the primary SARS-CoV-2 mRNA vaccination series with those who also received a booster vaccination and those who were unvaccinated. The authors found that vaccination was associated with lower rates of COVID-19 and adverse birth outcomes, including preterm birth, stillbirth, and very low birthweight neonates. Receipt of a booster dose was associated with even greater reductions in rates of COVID-19 and stillbirth than the primary series alone.
Establishing a Lancet Oncology Commission on the humanitarian crisis of cancer
Authors: Gary Rodin, Mac Skelton, Nirmala Bhoo-Pathy, Omar Dewachi, Madeline Li, Dario Trapani, Elizabeth Smyth, Matthew Banegas, Naveen Salins, Karla Unger-Saldaña, Camilla Zimmermann, Richard Sullivan
Journal: The Lancet Oncology (2023)
Cardiovascular Effects of GnRH Antagonists Compared With Agonists in Prostate Cancer
Authors: Adam J. Nelson, Renato D. Lopes, Hwanhee Hong, Kaiyuan Hua, Susan Slovin, Sean Tan, Jan Nilsson, Deepak L. Bhatt, Shaun G. Goodman, Christopher P. Evans, Noel W. Clarke, Neal D. Shore, David Margel, Laurence H. Klotz, Bertrand Tombal, Darryl P. Leong, John H. Alexander, Celestia S. Higano
Journal: JACC CardioOncology (2023)

Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists.
Does Acid Stress Cause Vascular Dysfunction?
Authors: Donald E. Wesson
Journal: Journal of the American Society of Nephrology (2023)

Department of Internal Medicine, Dell Medical School – The University of Texas at Austin, Austin, Texas Correspondence: Dr. Donald E. Wesson, Dell Medical School – The University of Texas at Austin, 1501 Red River Street, MC: ZO100, Austin, TX 78712. E-mail: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See related article, "Sodium Bicarbonate Treatment and Vascular Function in CKD: A Randomized, Double-Blind Placebo Controlled Trial," on pages 1433–1444.
Renal Function and the Adverse Maternal and Fetal Outcomes: New Evidence
Authors: Shiyuan Wei, Zhenbo Ouyang, Liangzhi Wu
Journal: Journal of the American Society of Nephrology (2023)

We appreciate the article by Tangren et al.1 and read it with great interest. The authors conducted a large, retrospective cohort study of 462,053 women with 565,907 pregnancies. The study found that low eGFR with concurrent proteinuria was associated with increased risk of adverse pregnancy outcomes. We congratulate the authors for the successful article and would like to make some comments. First, previous studies have shown that CKD was associated with a higher risk of adverse pregnancy outcomes,2 and this study yielded a similar conclusion with various categories of eGFR and proteinuria. Of note, in clinical practice, many women often consult about the effect of renal function on pregnancy outcomes, especially in women with abnormally elevated serum creatinine (SCr) or eGFR <60 ml/min per 1.73 m2. They are mainly concerned about two issues. First, what effect a low eGFR will have on pregnancy outcomes? Second, whether pregnancy will accelerate the progression of kidney disease? However, this article only focused on the first question. Much of the previous literature3 about the second issue indicated that women with preexisting kidney disease risked more rapid progression to kidney failure or eGFR decline if they became pregnant. However, these studies were single-center or case reports with less number of participants. Thus, it is still necessary to clarify the association of pregnancy with the progression of CKD using a large cohort. Second, although the outcome of AKI was rare in women with advanced CKD in this study, we still cannot ignore it. We should pay attention not only to preconception kidney function but also to changes in SCr levels during pregnancy. Glomerular hyperfiltration is a typical physiological adaptation to early pregnancy, and consequently, SCr concentrations decline in the first trimester, plateau in the second, and increase in the third trimester.4 Although creatinine-based equations used to estimate GFR accurately reflect the physiological changes in renal function during pregnancy, Kidney Disease Improving Global Outcomes criteria for AKI may miss some cases. Creatinine values in the third trimester that are modestly elevated from the baseline may reflect a substantial fall in GFR from the normal expected level of hyperfiltration. It is possible, but unknown, whether cystatin-C–based eGFR estimation will be useful in this setting. In addition, to date, it is still unknown whether AKI onset during pregnancy has a poor prognosis for the newborn. In summary, we constantly obtain new evidence regarding the relationship between renal function and maternal/fetal outcomes, but we still face challenges.
Non-invasive estimation of mean pulmonary artery pressure by cardiovascular magnetic resonance in under 2 min scan time
Authors: Goran Abdula, Joao G Ramos, David Marlevi, Alexander Fyrdahl, Henrik Engblom, Peder Sörensson, Daniel Giese, Ning Jin, Andreas Sigfridsson, Martin Ugander
Journal:  (2023)

Abstract Aims Non-invasive estimation of mean pulmonary artery pressure (mPAP) by cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow analysis has shown excellent agreement with invasive right heart catheterization. However, clinical application is limited by relatively long scan times. Therefore, the aim of this study was to evaluate the accuracy and time reduction of compressed sensing (CS) accelerated acquisition for mPAP estimation. Methods and results Patients (n = 51) referred for clinical CMR at 1.5 T or 3 T underwent imaging with both a prototype CS-accelerated and a non-CS-accelerated flow sequence acquiring time-resolved multiple 2D slice phase-contrast three-directional velocity-encoded images covering the pulmonary artery. Prototype software was used for the blinded analysis of pulmonary artery (PA) vortex duration to estimate mPAP as previously validated. CS-accelerated and non-CS-accelerated acquisition showed increased mPAP in 22/51 (43%) and 24/51 (47%) patients, respectively. The mean bias for estimating mPAP between the two methods was 0.1 ± 1.9 mmHg and the intraclass correlation coefficient was 0.97 (95% confidence interval 0.94–0.98). Effective scan time was lower for the CS-accelerated acquisition (1 min 55 s ± 27 s vs. 9 min 6 s ± 2 min 20 s, P &amp;lt; 0.001, 79% reduction). Conclusions CS-accelerated CMR acquisition enables preserved accuracy for estimating mPAP compared to a non-CS-accelerated sequence, allowing for an average scan time of less than 2 min. CS-acceleration thereby increases the clinical utility of CMR 4D flow analysis to estimate mPAP.
Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138
Authors: Jort J. van der Schans, Ziyu Wang, Jennemiek van Arkel, Thijs van Schaik, Afroditi Katsarou, Ruud Ruiter, Thomas Baardemans, Huipin Yuan, Joost de Bruijn, Sonja Zweegman, Niels W.C.J. van de Donk, Richard W.J. Groen, Maria Themeli, Tuna Mutis
Journal: Clinical Cancer Research (2023)

The success of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells illustrates the potential of this novel therapy for multiple myeloma. Nonetheless, broadening CAR T-cell therapy beyond BCMA requires inventive strategies as there are only a few multiple myeloma- or plasma cell-specific target antigens. We investigated the feasibility of achieving multiple myeloma specificity by dual-split CD38/CD138 CAR targeting, whereby the stimulatory and costimulatory signals for T-cell activation are split into two separate stimulatory (sCAR) and costimulatory CARs (cCAR).Using various combinations of CD38 and CD138 sCARs and cCARs with different affinities, we generated several dual-split CAR T cells and analyzed them for multiple myeloma-specific effector functions in vitro. The best-functioning CAR T cells were tested in vivo in a murine xenograft model.We found optimal designs of both CD38sCAR/CD138cCAR and CD138sCAR/CD38cCAR combinations, that effectively lysed multiple myeloma cells but spared single CD38- or CD138-positive healthy hematopoietic cells. While the CD38sCAR/CD138cCAR T cells achieved multiple myeloma-specific activity solely due to the low affinity of the CD38sCARs, the multiple myeloma-specific cytotoxicity, cytokine release, and proliferation of CD138sCAR/CD38cCAR T cells were established through a true combinatorial stimulatory and costimulatory effect. The most optimal combination comprised a low-affinity CD138sCAR combined with a high-affinity CD38cCAR. These CD138sCAR/CD38cCAR T cells also showed dual-antigen specific anti-multiple myeloma effects in vivo. Importantly, they were also effective against multiple myeloma cells from daratumumab pretreated patients with decreased CD38 expression levels.We demonstrate the possibility to specifically target multiple myeloma cells, even after CD38 targeted therapy, with carefully-designed dual-split CARs directed against CD38 and CD138.